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The Essential Guide to Menopause and Inflammation

Updated: Jan 1

Discover the connection between menopause and inflammation, how a decline in ovarian hormones impacts your immune system and contributes to the development chronic diseases.


Menopause is the phase in a woman's life, where the menstrual cycle stops due to a decline in hormonal function of the ovaries. This decline in ovarian hormone function increases systemic inflammation in the body and in the central nervous system. The interplay between menopause and inflammation raises important questions about the impact on our health and longevity.


What is inflammation?


Acute inflammation is the body's short-term immune response to infection or injury. It is a complex process that involves the release of chemicals and immune cells to protect the body and aid in tissue repair.


Inflammation can become chronic or dysregulated. When this happens, instead of helping the body to heal, inflammation creates tissue damage. Inflammation is the underlying process behind most chronic diseases such as depression, cardiovascular disease, autoimmune disorders, and cancers.





Chronic Inflammation and Inflammaging


As you age, your body's ability to regulate inflammation decreases. This leads to a state of chronic inflammation, known as "inflammaging". Inflammaging is associated with an increase in pro-inflammatory markers and a decrease in anti-inflammatory markers in the body. It contributes to the development of various age-related diseases.


External influences to the body can accelerate inflammation and these associated diseases.


Risk factors that accelerate inflammaging include:

  • toxin exposure such as smoking, alcohol, air pollution and food additives,

  • lack of physical activity,

  • chronic stress such as financial stress, racism, violence, discrimination,

  • inflammatory diet: high sugar, high seed oil, processed meats, ultra-processed foods.


Menopause and Inflammation aka Inflammopause


During perimenopause and menopause, the fluctuating and declining estrogen levels cause an accelerated shift in the balance of pro-inflammatory and anti-inflammatory cytokines, leading to a low-grade increase in inflammation.


This shift towards a pro-inflammatory state with declining hormone levels associated with perimenopause and menopause has been coined "inflammopause" (Inflamm-aging or inflamm-opause).


Inflammopause is associated with an increased risk in inflammatory conditions seen in women around this age including:

  • autoimmune conditions such as Hashimoto's thyroiditis & rheumatoid arthritis,

  • perimenopausal mood changes, depression

  • the beginnings of the development of atherosclerosis and dementia which often begin in midlife.


Women can spend more than half their life as postmenopausal women. It is essential that women understand how the low ovarian hormonal state contributes to inflammation and chronic disease.



Low Ovarian Hormones and Inflammation


Perimenopause and menopause are a result of endocrine aging. The low hormone levels contribute to inflammation in the following ways:


Estradiol and Inflammation


Estradiol is the queen regulator of immune function and reducing inflammation. It is neuro-protective, cardio-protective and strengthens bones. Estradiol is primarily produced by the ovaries, so after menopause estradiol levels are low.


The main estrogen in the body after menopause is estrone, produced primarily by adipose cells (fat cells) and this type of estrogen is proinflammatory.


Low estrogen levels triggers the immune system to produce pro-inflammatory cytokines or chemical messengers (Understanding how we age: insights into inflammaging)


Lower estrogen levels correlates to higher homocysteine levels and other inflammatory markers (Inflammation and Sex Hormones in Postmenopausal Women).


Progesterone and Inflammation


Progesterone also plays a role in decreasing inflammation. Progesterone levels fall in perimenopause as cycles become anovulatory (no ovulation occurs).


Progesterone inhibits the production of proinflammatory cytokines such as TNF-α, IFN-γ, and IL-12. It also promotes the production of anti-inflammatory cytokines, including IL-10 (Progesterone-based compounds affect immune responses).


Because progesterone has beneficial anti-inflammatory and immunomodulatory effects, it has been proposed as the steroid of choice when treating chronic inflammatory and autoimmune diseases, including endometriosis, stress-related disorders, rheumatoid arthritis, and miscarriages in women (Progesterone as an Anti-Inflammatory Drug and Immunomodulator).


It is also for this reason that progesterone/progestogens are used in recovery from:

Testosterone and Inflammation


Testosterone, depending on the levels can have pro or anti-inflammatory effects.


At levels higher than the typical female physiological range, testosterone promotes higher insulin secretion, insulin resistance, metabolic dysfunction and inflammation. This is in part why women with PCOS are at increased risk of inflammatory disorders such as cardiovascular disease and depression.


Androgens in the typical female physiological range are thought to exhibit immunosuppressive effects via stimulating the formation of lipid mediators (from polyunsaturated fatty acids) in immune cells (Impact of Androgens on Inflammation, 2020).



Cytokines, Menopause and Inflammation


Cytokines are signalling molecules that are produced by cells in the immune system. They are inflammation markers and play a pivotal role in inflammaging—the chronic, low-grade inflammation associated with ageing.


These molecules are involved in various processes within the immune system and can contribute significantly to the inflammatory state observed in inflammaging.


Increased Production of Pro-inflammatory Cytokines


With ageing and with menopause there is often a shift in the immune system's balance, leading to a state where the body produces more pro-inflammatory cytokines, such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1β) and C reactive protein (CRP) (Changes in Proinflammatory Cytokine Activity after Menopause, 2002).


Important cytokines that become elevated during perimenopause and menopause include;

Menopausal Impacts on Metabolism


Hormonal variability during perimenopause and low hormones postmenopausal contributes to a number of further factors which increase inflammation. These include;


  • Higher cholesterol or inflammatory cholesterol ratios (dyslipidaemia),

  • Insulin resistance,

  • Adipose tissue redistribution around and within the organs,

  • Loss of muscle mass

  • Sleep Impairment

  • Increased cortisol.


Brain-Inflammation and Menopause


Brain-inflammation is particularly problematic. It can contribute to cognitive decline and neurodegenerative diseases. This phenomenon known as neuro-inflammation is closely linked to menopause, with estrogen depletion being a significant contributor.


Studies have shown that estrogen plays an essential role in regulating inflammation in the brain.


It modulates the activity of microglial cells (immune cells in the brain), which are responsible for initiating the inflammatory response in the central nervous system (Estrogens, Neuroinflammation, and Neurodegeneration).


Perimenopause is a proinflammatory state that disrupts estrogen-regulated neurological systems. (peri-menopause in a woman’s life: a systemic inflammatory phase)


In addition to causing low-grade systemic body inflammation, perimenopause also contributes to low-grade central nervous system inflammation, creating a variety of of neurological symptoms from:


  • Temperature dysregulation in the brain: causing hot flashes and night sweats

  • Autonomic dysfunction in the brain contributing to palpitations and high blood pressure,

  • Mood dysregulation causing irritability, low mood, anxiety

  • Memory issues and difficulties with executive function creating the experience of brain fog.



The menopausal transition can last more than a decade. Over the long term these neurological inflammatory changes, particularly those impacted by more severe hot flashes during perimenopause may be associated with increased risks of stroke and neuro-degenerative diseases such as Alzheimer's (Menopausal Vasomotor Symptoms and White Matter Hyperintensities in Midlife Women, 2023).


This research linking brain inflammation, perimenopause/menopause and dementia is emerging and over the next decade I hope there is a lot more data for women as to how to best prevent dementia.


Effects of Inflammation During Menopause


Bone Health


The decline in ovarian hormone function at menopause is associated with an increase in pro inflammatory cytokines. These pro-inflammatory cytokines: IL-1 and IL-6, TNF and IFN promote increased bone breakdown by cells called osteoclasts. This results in the thinning of the bones (osteopenia followed by osteoporosis).


Thin bones increase the risk of fracture from falls and fracture without injury, both of which limit mobility and quality of life.


Cardiovascular Health


Menopause-related inflammation contributes to artherosclerosis, the process of cholesterol deposition and immune inflammation within the walls of the arteries. This process leads to a number of diseases such as heart attacks, strokes and peripheral vascular disease.


Cognitive Function


As discussed above, inflammation during menopause likely plays a role in conditions like stroke, Alzheimer's disease and other forms of dementia.


Brain inflammation is also the underlying dysfunction in depression and anxiety.


Metabolic health


Low estrogen promotes insulin resistance and metabolic dysfunction. Diabetes and metabolic syndrome are more common in women post menopause.


The ZOE PREDICT trial 2022 demonstrated that post menopausal women had higher fasting glucose, HBA1C and markers of inflammation compared with premenopausal women.


They also showed poorer metabolic function after eating with higher glucose and insulin responses after meals compared with premenopausal women.


Managing Inflammation During Menopause


Reducing inflammaging involves adopting a healthy lifestyle, including a whole food diet containing diverse plant foods, regular exercise, stress management, and avoiding smoking. Additionally, certain anti-inflammatory foods, supplements, and medications may help to promote healthier ageing.


Healthy Lifestyle Changes





Anti-Inflammatory Diet


Eat a balanced anti-inflammatory whole food diet rich in:


  • colourful fruits, such as berries, citrus fruits, kiwifruit, avocado and apples

  • colourful vegetables such as spinach, broccoli, kale, pumpkin, beetroot, carrots, kūmara

  • whole grains such as buckwheat, brown rice and quinoa,

  • fatty fish like salmon, mackerel, tuna and sardines

  • legumes such as beans, lentils and chickpeas

  • nuts and seeds including walnuts, almonds, chia seeds and flaxseeds,

  • herbs such as turmeric, ginger, cinnamon and garlic

  • healthy fats such as extra virgin olive oil, avocados, coconut oil

  • spices such as ginger, cinnamon, turmeric

  • teas such as green tea, matcha and herbal teas like ginger, chamomile and peppermint


Regular consumption of these can help lower inflammation levels in the body. These foods contain antioxidants, phytonutrients, magnesium and healthy fats to support a healthy inflammatory response.


They also promote the proliferation of healthy gut bacteria such as lactobacillus and bifidobacteria that promotes lower inflammation in the body.





Regular Exercise


Engaging in moderate physical activities produces a number of powerful antioxidants and anti-inflammatory compounds such as nitric oxide and endocannabinoids that can help reduce inflammation and improve overall health.


Regular exercise can also help maintain muscle mass and bone density. It also improves insulin senstivity. It also promotes better sleep, which can further contribute to managing inflammation during menopause.


Stress Management


Chronic stress increases hormones such as cortisol, epinephrine and norepinephrine which trigger inflammation levels in the body.


There are many practices which reduce the stress reaction in the body. These include:

  • mindfulness meditation,

  • yoga,

  • breathing techniques

  • spending time in nature,

  • cold water swimming/showers

  • chanting, singing, dancing

Develop a daily practice to manage stress well, reduce stress and promote overall well-being.


Avoiding Smoking and Alcohol


Smoking is a significant contributor to chronic inflammation. Quitting smoking can significantly improve overall health and reduce inflammation levels in the body.


Alcohol consumption increases inflammation in the body and is a direct carcinogen for multiple cancers including breast cancer, liver cancer, bowel cancer (WHO, Alcohol Carcinogenic).


Limiting or avoiding alcohol can reduce inflammation and support a healthier menopause transition.



Hormone Replacement Therapy and Inflammopause


Hormone Replacement Therapy (HRT) is often prescribed to alleviate menopausal symptoms such as hot flashes, mood changes, joint pain and vaginal dryness. It works by replacing the hormones that fluctuate and decline during menopause.


However, HRT, especially transdermal estrogen therapy, has also been shown to decrease inflammation and can potentially reduce the risk of chronic diseases associated with ovarian hormone decline and menopausal inflammation.


Women who experience surgical menopause or premature ovarian failure (early or premature menopause) are at increased risk of the impacts of early inflammation and associated diseases such as dementia, stroke, diabetes, heart failure and heart disease (Early Menopause and Cardiovascular Disease Risk, 2021).


It is especially important that these women are offered adequate hormone therapy (See ESHRE Guideline on the management of premature ovarian insufficiency)


The benefits of using menopausal hormone therapy seem to be most significant when started during perimenopause to mitigate fluctuating hormonal fluxes or early post menopausal hormone therapy to avoid a state of low hormones that is proinflammatory.


Current evidence suggests that when women start postmenopausal hormone therapy over a decade after menopause, they may experience relief from the symptoms of low hormones. However, they may not experience the anti-inflammatory gains that is seen when women start hormone therapy at earlier ages. This is because they have lived a for over a decade in which the proinflammatory disease processes have been underway (The Timing Hypothesis: Hormone Therapy, 2018).


The risks of menopause hormone therapy have been overstated and the benefits have been understated. Since the early 2000s women have been scared away from using menopause hormone therapy, a treatment that not only improves quality of life in terms of symptom relief, but also reduces long-term disease risk and promotes healthy aging.
It's time for change.

- Dr Deborah Brunt, Menopause Doctor




Inflammation and Menopause: In Summary


Understanding the relationship between inflammation and menopause is crucial for adequate healthcare provision to women during the perimenopause and beyond and to facilitate optimal ageing for women.


Menopause-associated inflammation can be mitigated by healthy lifestyle practices AND the use of menopause hormone therapy.


Consult with your healthcare providers for personalised advice and management strategies tailored to your unique health needs.

_______


Dr Deborah Brunt is a women's health and menopause doctor in Dunedin, New Zealand and also provides menopause health coaching internationally to support optimal health habits for aging well so you can live your best life.


Schedule a free discovery call with her to learn more about how she could support you with your unique health situation.



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